Optimization of cytarabine (ARA-C) therapy for acute myeloid leukemia.
Optimization of cytarabine (ARA-C) therapy for acute myeloid leukemia.
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DOI：
10.1186/2162-3619-2-20
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发表时间：
2013
影响因子：
10.9
通讯作者：
Momparler RL
中科院分区：
文献类型：
--
作者：
Momparler RL
阿糖胞苷（阿糖胞苷）是治疗急性髓系白血病最有效的药物之一。用于治疗这种白血病的阿糖胞苷的标准剂量是每平方米 100 毫克。为了提高阿糖胞苷对抗急性髓系白血病的有效性，在治疗中引入了高剂量治疗（3,000 毫克/平方米）。大剂量阿糖胞苷的副作用是一个主要问题，尤其是其神经毒性。最近的临床试验回顾表明，这种高剂量阿糖胞苷可以用每平方米1000毫克的中剂量替代，且不会丧失疗效，且毒性较小。这是提高阿糖胞苷治疗急性髓系白血病疗效的重要一步。尽管这种白血病的治疗方法有所改进，但目前成年患者的总生存率还不到 30%。为了优化阿糖胞苷治疗，重要的是确定一些白血病干细胞如何在治疗中存活。临床前数据表明，白血病干细胞的存活可能是由于阿糖胞苷输注之间长达 12 小时的间隔，这使得一些白血病细胞能够逃避其 S 期特异性作用。导致白血病细胞存活的其他因素包括肝脏和脾脏中胞苷脱氨酶（一种使阿糖胞苷失活的酶）水平较高，以及由于脱氧胞苷激酶（一种激活前药阿糖胞苷的酶）缺乏而产生的耐药性。本评论提出了几种方法来克服这些障碍，目的是提高阿糖胞苷治疗急性髓系白血病的有效性。
Cytarabine (cytosine arabinoside) is one of the most effective drugs for the treatment of acute myeloid leukemia. The standard dose of cytarabine used to treat this leukemia is 100 mg per square meter. In an attempt to improve the effectiveness of cytarabine against acute myeloid leukemia, a high-dose treatment (3,000 mg per square meter) was introduced into therapy. The side effects of high-dose cytarabine was a major concern, especially its neurological toxicity. A review of recent clinical trials indicates that this high-dose cytarabine can be replaced by the intermediate-dose of 1,000 mg per square meter without loss of efficacy and with less toxicity. This is an important step to improve the efficacy of cytarabine for the treatment of acute myeloid leukemia. Despite the improvements in the therapy for this leukemia, the current overall survival rate for adult patients is less than 30%. To optimize the cytarabine therapy, it is important to determine how some leukemic stem cells survive treatment. Preclinical data suggest that survival of the leukemic stem cells could be due to the long 12 hour interval between infusions of cytarabine, which permits some leukemic cells to escape its S phase specific action. Among the other factors that can lead to leukemic cell survival are the high levels in the liver and spleen of cytidine deaminase, the enzyme that inactivates cytarabine and drug resistance due to deficiency in deoxycytidine kinase, the enzyme that activates the prodrug, cytarabine. Several approaches are proposed in this commentary to overcome these impediments with the goal of increasing the effectiveness of cytarabine for the treatment of acute myeloid leukemia.